Bacterial toxins

1. Bacterial Toxins
Classification
Dr.Faghri
Meisam.Roozbahani

2. Introduction
 Toxins were the first bacterial virulence factors to
be identified and were also the first link between
bacteria and cell biology.

3. Introduction
 Cellular microbiology was, in fact, naturally born
a long time ago with the study of toxins, and only
recently, thanks to the sophisticated new
technologies, has it expanded to include the study
of many other aspects of the interactions
between bacteria and host cells.

4. Two Main Categories of Toxins

7. Specific Host Site Exotoxins
 Neurotoxins
 Enterotoxins
 Cytotoxins
 Nephrotoxin
 Hepatotoxin
 Cardiotoxin

8. Classification by Entrance Mechanism

9. Acting on
intracellular
targets
Injected into
eukaryotic cells
Unknown
mechanism of
action
Acting on the
cell surface
Immune system
(Superantigens)
Class
Target
Surface molecules
Cell membrane
Large pore- forming toxins
Small pore- forming toxins
Insecticidal toxins
Membrane-perturbing
toxins
Other pore- forming
toxins
RTX toxins
Protein synthesis Mediators of apoptosis
Signal transduction
Cytoskeleton structure
Intracellular trafficking
Inositol phosphate
metabolism
Cytoskeleton
Signal transduction

10. Toxins acting on the cell surface:
Immune system (Superantigens)
 Superantigens are bacterial
and viral proteins that share
the ability to activate a large
fraction of T-lymphocytes.

11. Toxins acting on the cell surface: Immune system (Superantigens)
Toxin Organism Activity Consequence
SEA-SEI, TSST-1, SPEA,
SPEC, SPEL, SPEM, SSA, and
SMEZ
Staphylococcus
aureus and Streptococcus
pyogenes
Binding to MHC class II
molecules and to Vβ or Vγ
of T cell receptor
T cell activation and
cytokines secretion
MAM
Mycoplasma
arthritidis
Binding to MHC class II
molecules and to Vβ or Vγ
of T cell receptor
Chronic inflammation
YPMa
Yersinia
pseudotuberculosis
Binding to MHC class II
molecules and to Vβ or Vγ
of T cell receptor
Chronic Inflammation
SPEB S. pyogenes Cysteine protease
Alteration in
Immunoglobulin binding
properties
ETA, ETB, and ETD S. aureus
Trypsin-like serine
proteases
T-cell proliferation,
intraepidermal layer
separation

12. Agr Regulatory System

13. Toxins acting on the cell surface:
Surface molecules
 BFT enterotoxin: The pathogenicity of ETBF is
ascribed to a heat-labile ∼20-kDa toxin (B.
fragilis toxin [BFT], also called fragilysin).
 This toxin binds to a specific intestinal epithelial
cell receptor and stimulates cell proliferation.

14. BFT enterotoxin

15. Toxins acting on the cell surface: Surface molecules
Toxin Organism Activity Consequence
BFT enterotoxin Bacteroides fragilis Metalloprotease, cleavage
of E-cadherin
Alteration of epithelial
permeability
AhyB Aeromonas
hydrophyla
E l a s t a s e ,
metalloprotease
Hydrolization of casein and
elastine
Aminopeptidase Pseudomonas
aeruginosa
E l a s t a s e ,
metalloprotease
Corneal infection,
inflammation and
ulceration
ColH Clostridium
histolyticum
Collagenase,
metalloprotease
Collagenolytic activity
Nhe Bacillus cereus Metalloprotease and
collagenase
Collagenolytic activity

16. Toxins acting on the cell surface:
Pore-Forming
 Protein toxins forming pores in biological membranes
occur frequently in Gram-positive and Gram-negative
bacteria.
 Pore-forming toxins, also known as "lytic factors".
 Some of them are also called "hemolysins“.

17. Toxins acting on the cell surface:
Large Pore-Forming Toxins
 Generally secreted by diverse species of Gram-
positive bacteria.
 Binding selectively to cholesterol on the
eukaryotic cell membrane.

18. Toxins acting on the cell surface: Large pore forming toxins
Toxin Organism Activity Consequence
PFO C. perfringens
Thiol-activated cytolysin,
cholesterol Binding
Gas gangrene
SLO S. pyogenes
Thiol-activated cytolysin,
cholesterol Binding
Transfer of other toxins,
cell death
LLO
Listeria monocytogenes
Induction of Lymphocyte
apoptosis
Membrane damage
Pneumolysin S. pneumoniae
Induction of Lymphocyte
Apoptosis
Complement activation,
cytokine production,
apoptosis

19. Toxins acting on the cell surface:
Small pore forming toxins
 Creating very small pores 1-1.5 nm diameter.
 Selective permeabilization to solutes with a molecular
mass less than 2 kDa.

20. Toxins acting on the cell surface: Small pore forming toxins
Toxin Organism Activity Consequence
Alveolysin B. alveis Induction of lymphocyte Apoptosis
Complement activation, cytokine
production, apoptosis
ALO B. anthracis Induction of lymphocyte apoptosis
Complement activation, cytokine
production, Apoptosis
α-Toxin S. aureus Binding of erythrocytes Release of cytokines, cell lysis, apoptosis
PVL leukocidin
(LukS-LukF)
S. aureus Cell membrane permeabilization
Necrotic enteritis, rapid shock-like
syndrome
γ-Hemolysins
(HlgA- HlgB and
HlgC- HlgB)
S. aureus Cell membrane permeabilization
Necrotic enteritis, rapid shock-like
syndrome
β-Toxin C. perfringens Cell membrane permeabilization Necrotic enteritis, neurologic effects

21. Toxins acting on the cell surface:
RTX toxins
 The RTX toxin family is a group of cytotoxins produced by
Gram-negative bacteria.
 There are over 1000 known members with a variety of
functions.

22. Toxins acting on the cell surface:
RTX toxins
 The RTX family is defined by two common features:
characteristic repeats in the toxin protein sequences, and
extracellular secretion by the type I secretion system
(T1SS).
 The name RTX (repeats in toxin) refers to the glycine and
aspartate-rich repeats located at the C-terminus of the
toxin proteins.

23. Genomic Structure
 The toxin is encoded by four genes, one of which, hlyA,
encodes the 110-kDa hemolysin. The other genes are
required for its posttranslational modification (hlyC) and
secretion (hlyB and hlyD).

24. Toxins acting on the cell surface: RTX toxins
Toxin Organism Activity Consequence
Hemolysin II B. cereus Cell membrane permeabilization Hemolytic activity
CytK B. cereus Cell membrane Permeabilization Necrotic enteritis
HlyA E. coli Calcium-dependent formation of transmembrane Pores Cell permeabilization and lysis

25. Toxins acting on the cell surface:
Membrane perturbing toxins
 Soap like structure.
 The toxin binds nonspecifically parallel to the surface of
any membrane without forming transmembrane channels.
 Cells first become permeable to small solutes and
eventually swell and lyse, releasing cell intracellular
content.

26. Toxins acting on the cell surface: Membrane perturbing toxins
Toxin Organism Activity Consequence
ApxI, ApxII, and ApxIII A.pleuropneumoniae
Calcium-dependent formation of
transmembrane Pores
Lysis of erythrocytes and
other nucleated Cells
LtxA A.actinomycetemcomitans
Calcium-dependent formation of
transmembrane Pores
Apoptosis
LtxA P.Haemolytica
Calcium-dependent formation of
transmembrane Pores
Activity specific versus
ruminant leukocytes

27. Toxins acting on the cell surface:
Other pore forming toxins
 Like other functionally related toxins, aerolysin changes
its topology in a multi-step process from a completely
water-soluble form to a membrane-soluble heptameric
transmembrane channel that destroys sensitive cells by
breaking their permeability barriers.

28. Toxins acting on the cell surface: Other pore forming toxins
Toxin Organism Activity Consequence
δ-Hemolysin S. aureus Perturbation of the lipid bilayer Cell permeabilization and lysis
Aerolysin A. hydrophila Perturbation of the lipid bilayer Cell permeabilization and lysis
AT C. septicum Perturbation of the lipid bilayer Cellpermeabilization and lysis

29. Toxins acting on the cell surface:
Insecticidal toxins
 The class of insecticidal proteins, also known as
δ-endotoxins, includes a number of toxins produced by
species of Bacillus thuringiensis.
 These exert their toxic activity by making pores in the
epithelial cell membrane of the insect midgut.

30. Toxins acting on the cell surface:
Insecticidal toxins
 δ-Endotoxins form two multigenic families, cry and cyt;
 members of the cry family are toxic to insects of
Lepidoptera, Diptera and Coleoptera orders (Hofmann et al.,
1988),
 whereas members of the cyt family are lethal specifically to
the larvae of Dipteran insects (Koni and Ellar, 1994).
Lepidoptera is a large order of insects that includes moths and butterflies.
True flies are insects of the order Diptera.
Coleoptera is an order of insects commonly called beetles.

31. Toxins acting on the cell surface: Insecticidal toxins
Toxin Organism Activity Consequence
PA B. anthracis Perturbation of the lipid bilayer Cell permeabilization and lysis
HlyE E. coli Perturbation of the lipid bilayer Osmotic lysis of cells lining the Midgut
CryIA, CryIIA,
CryIIIA, etc
Bacillus thuringiensis
Destruction of the transmembrane
Potential
Osmotic lysis of cells lining the Midgut
CytA, CytB B. thuringiensis
Destruction of the transmembrane
Potential
Osmotic lysis of cells lining the Midgut
BT toxin B. thuringiensis
Destruction of the transmembrane
Potential
Cytocidal activity on human cells

32. Toxins Acting on Intracellular Targets
 The group of toxins with an intracellular
target (A/B toxins) contains many toxins
with different structures that have only
one general feature in common: they are
composed of two domains generally
identified as "A" and "B.“
Acting on
intracellular
targets
Injecte
eukaryo
Acting on the
cell surface
Immune system
(Superantigens)
Class
arget
Surface molecules
Cell membrane
Large pore- forming toxins
Small pore- forming toxins
Protein synthesis Mediators o
Signal transduction
Cytoskeleton structure
Intracellular trafficking
Inositol ph
metab
Cytoske
Signal tran

33. Toxins Acting on Intracellular Targets
 The A domain is the active portion of the toxin; it usually
has enzymatic activity and can recognize and modify a
target molecule within the cytosol of eukaryotic cells.
 The B domain is usually the carrier for the A subunit; it
bind the receptor on the cell surface and facilitates the
translocation of A across the cytoplasmic membrane.

34. Toxins acting on intracellular targets:
Protein synthesis
 These toxins are able to cause rapid cell death at
extremely low concentrations.
 This reaction leads to the formation of a completely
inactive EF2-ADP-ribose complex.

35. Toxins acting on intracellular targets:
Protein synthesis
 A very important step in the elucidation of the mechanism
of enzymatic activity has been the determination of the
crystal structure for the complex of diphtheria toxin with
NAD.
 Upon the addition of NAD to nucleotide-free DT crystals, a
significant structural change.
 This change lead to recognition and binding of the
acceptor substrate EF-2.
 This would explain why DT recognizes EF-2 only after NAD
has bound.

36. Toxins acting on intracellular targets:
Protein synthesis
Toxins acting on intracellular targets: Protein synthesis
Toxin Organism Activity Consequence
DT Corynebacterium diphtheriae ADP-ribosylation of EF-2 Cell death
PAETA P. aeruginosa ADP-ribosylation of EF-2 Cell death
SHT S. dysenteriae N-glycosidase activity on 28S RNA Cell death, apoptosis

37. Toxins acting on intracellular targets:
Signal transduction
 Two types of transduction mechanism:
 Tyrosine phosphorylation
 Modification of a receptor-coupled GTP-binding protein
 cyclic AMP
 inositol triphosphate
 diacylglycerol

38. Pertussis toxin
PT Subunits
A
B

39. Cholera toxin (CT) and E. coli heat-
labile enterotoxins (LT-I and LT-II)
 Cholera toxin (CT) and E. coli heat-labile enterotoxins (LT-
I and LT-II) share an identical mechanism of action and
homologous primary and 3D structures.
 While V. cholerae exports the CT toxin into the culture
medium, LT remains associated to the outer membrane
bound to lipopolysaccharide.
 The corresponding genes of CT and LT are organized in a
bicistronic operon and are located on a filamentous
bacteriophage and on a plasmid, respectively.

40. Clostridium difficile Toxins
 Enterotoxin A (TcdA) and cytotoxin B (TcdB) of Clostridium
difficile are the two virulence factors responsible for the
induction of antibiotic-associated diarrhea.
 The toxin genes tcdA and tcdB together with three
accessory genes (tcdC-E) constitute the pathogenicity
locus (PaLoc) of C. difficile.

41. Toxins acting on intracellular targets: Signal transduction 1
Toxin Organism Activity Consequence
PT Bordetella pertussis ADP-ribosylation of Gi cAMP increase
CT Vibrio cholerae ADP-ribosylation of Gi cAMP increase
LT E. coli ADP-ribosylation of Gi cAMP increase
α-Toxin (PLC) C. perfringens Zinc-phospholipase C, hydrolase Gas gangrene
Toxins A and B (TcdA and
TcdB)
C. difficile
Monoglucosylation of Rho, Rac,
Cdc42
Breakdown of cellular actin
stress fibers
Adenylate cyclase (CyaA) B. pertussis
Binding to calmodulin ATP→cAMP
conversion
cAMP increase

42. Anthrax Edema and Lethal Factors
 The EF and LF genes are located on a large plasmids.
 Cleavage of the N-terminal signal peptides yields mature
EF and LF proteins.
 LF, is able to cause apoptosis in human endothelial cells.

43. E. coli Cytotoxin Necrotizing Factors and
Bordetella Dermonecrotic Toxin
 CNF1 & CNF2: produced by a number of uropathogenic
and neonatal meningitis-causing pathogenic E. coli
strains.
 cnf1 is chromosomally encoded, cnf2 is carried on a
large transmissible F-like plasmid called "Vir“.
 DNT is a transglutaminase, which causes alteration of
cell morphology, reorganization of stress fibers, and
focal adhesions on a variety of animal models.

44. Cytolethal Distending Toxins
 HdCDT is a complex of three proteins (CdtA, CdtB and
CdtC) encoded by three genes that are part of an operon.
 Members of this family have been identified in E. coli,
Shigella, Salmonella, Campylobacter, Actinobacillus and
Helicobacter hepaticus.

45. Toxins acting on intracellular targets: Signal transduction 2
Toxin Organism Activity Consequence
Anthrax edema factor (EF) B. anthracis
Binding to calmodulin ATP→cAMP
conversion
cAMP increase
Anthrax lethal factor (LF) B. anthracis Cleavage of MAPKK1 and MAPKK2 Cell death, apoptosis
Cytotoxin necrotizing
factors 1 and 2 (CNF1, 2)
E. coli Deamidation of Rho, Rac and Cdc42
Ruffling, stress fiber
formation.
DNT Bordetella species
Transglutaminase, deamidation or
polyamination of Rho GTPase
Ruffling, stress fiber
formation
CDT Several species
DNA damage, formation of actin
stress fibers via activation of RhoA
Cell-cycle arrest,
cytotoxicity, apoptosis

46. Toxins acting on intracellular targets:
Cytoskeleton structure
 The cytoskeleton is a cellular structure that consists of a
fiber network composed of microfilaments, microtubules,
and the intermediate filaments.
 It controls a number of essential functions in the
eukaryotic cell:
 exo- and endocytosis
 vesicle transport
 cell-cell contact
 and mitosis

47. Toxins acting on intracellular targets:
Cytoskeleton structure
 Most of them do it by modifying the regulatory, small G
proteins, such as Ras, Rho, and Cdc42, which control cell
shape.

48. Lymphostatin
 Lymphostatin is a very recently identified protein in
enteropathogenic strains of E. coli
 Lymphostatin selectively block the production of
interleukin-2, IL-4, IL-5 and γ interferon by human cells
and inhibit proliferation of these cells, thus interfering
with the cellular immune response.

49. Toxins acting on intracellular targets: Cytoskeleton structure
Toxin Organism Activity Consequence
Toxin C2 and related
proteins
C. botulinum ADP-ribosylation of monomeric G actin Failure in actin polymerization
Lymphostatin E. coli Block of interleukin production Chronic diarrhea
Iota toxin and related
proteins
C. perfringens Block of interleukin production Chronic diarrhea

50. Toxins acting on intracellular targets:
Intracellular trafficking
 Vesicle structures are essential in:
 receptor-mediated endocytosis
 and exocytosis
 One example of exocytic pathway is that involving the
release of neurotransmitters

51. Mechanism of action of clostridial
neurotoxins (CNT)
Synaptosomal-associated protein 25 (SNAP-25)

52. Helicobacter pylori Vacuolating
Cytotoxin Vac A
 This toxin is responsible for massive growth
of vacuoles within epithelial cells.
 VacA can insert into membranes forming
hexameric, anion-selective pores.

53. Toxins acting on intracellular targets: Intracellular trafficking
Toxin Organism Activity Consequence
TeNT C. tetanii Cleavage of VAMP/ synaptobrevin Spastic paralysis
BoNT-B, D, G and F
neurotoxins
C. botulinum Cleavage of VAMP/ synaptobrevin Flaccid paralysis
BoNT-A, E neurotoxins C. botulinum Cleavage of SNAP-25 Flaccid paralysis
BoNT-C neurotoxin C. botulinum Cleavage of syntaxin, SNAP-25 Flaccid paralysis
Vacuolating cytotoxin
VacA
H. pylori Alteration in the endocytic pathway
Vacuole formation,
apoptosis
NAD glycohydrolase S. pyogenes Keratinocyte apoptosis
Enhancement of GAS
proliferation

54. Toxins injected into eukaryotic cells
 These bacteria intoxicate individual eukaryotic cells by
using a contact-dependent secretion system to inject or
deliver toxic proteins into the cytoplasm of eukaryotic
cells.
 This is done by using specialized secretion systems that in
Gram-negative bacteria are called "type III" or "type IV,“.

55. Toxins injected into eukaryotic cells:
Mediators of apoptosis: IpaB in Shigella
 Shigella invasion plasmid antigen (Ipa) proteins: IpaA,
IpaB, IpaC, IpaD.
 Only IpaB is required to initiate cell death.
Acting on
intracellular
targets
Injected into
eukaryotic cells
Acting on the
cell surface
Immune system
(Superantigens)
Class
Target
Surface molecules
Cell membrane
Large pore- forming toxins
Small pore- forming toxins
Membrane-perturbing
toxins
RTX toxins
Protein synthesis Mediators of apoptosis
Signal transduction
Cytoskeleton structure
Intracellular trafficking
Inositol phosphate
metabolism
Cytoskeleton
Signal transduction

56. Toxins injected into eukaryotic cells:
Mediators of apoptosis: SipB in Salmonella
 An analog of Shigella invasin IpaB.
 In contrast to Shigella, Salmonella does not escape from
the phagosome, but it survives and multiplies within the
macrophages.
 Salmonella virulence genes are encoded by a chromosomal
operon named sip containing five genes (sipEBCDA).

57. Toxins injected into eukaryotic cells: Mediators of apoptosis
Toxin Organism Activity Consequence
IpaB Shigella Binding to ICE Apoptosis
SipB Salmonella Cysteine proteases Apoptosis
YopP/YopJ Yersinia species Cysteine protease, blocks MAPK and NFkappaB pathways Apoptosis

58. Toxins injected into eukaryotic cells:
Inositol phosphate metabolism
 SopB: in Salmonella is homologous to the Shigella flexneri
lpgD virulence factor.
 Both proteins contain two regions of sequence similarities
with human inositol polyphosphatases types I and II.

59. Toxins injected into eukaryotic cells: Inositol phosphate metabolism
Toxin Organism Activity Consequence
SopB
Salmonella
species
Inositol phosphate phosphatase, cytoskeleton
rearrangements
Increased chloride
secretion (diarrhea)
IpgD S. flexneri
Inositol phosphate phosphatase, cytoskeleton
rearrangements
Increased chloride
secretion (diarrhea)

60. Toxins injected into eukaryotic cells: Signal transduction
Toxin Organism Activity Consequence
ExoS P. aeruginosa ADP-ribosylation of Ras, Rho GTPase Collapse of cytoskeleton
C3 exotoxin C. botulinum ADP-ribosylation of Rho
Breakdown of cellular actin stress
fibers
EDIN-A, B and C S. aureus ADP-ribosylation of Rho Modification of actin cytoskeleton
SopE
S.
typhimurium
Rac and Cdc42 activation
Membrane ruffling, cytoskeletal
reorganization, proinflammatory
cytokines production
SipA
S.
typhimurium
Rac and Cdc42 activation
Membrane ruffling, cytoskeletal
reorganization, proinflammatory
cytokines production
IpaA
Shigella
species
Vinculin binding Depolymerization of actin filaments
YopE
Yersinia
species
GAP activity towards RhoA, Rac1 or Cdc42 Cytotoxicity, actin depolymerization
YopT
Yersinia
species
Cysteine protease, cleaves RhoA, Rac, and
Cdc42 releasing them from the membrane
Disruption of actin cytoskeleton
VirA
Shigella
flexneri
Inhibition of tubulin polymerization
Microtubule destabilization and
membrane ruffling

61. Toxins injected into eukaryotic cells: Signal transduction
Toxin Organism Activity Consequence
YpkA Yersinia species Protein serine/threonine kinase Inhibition of phagocytosis
YopH Yersinia species Tyrosine phosphatase Inhibition of phagocytosis
Tir E. coli EPEC Receptor for intimin Actin nucleation and pedestalformation
CagA H. pylori Tyrosine phosphorylated Cortactin dephosphorylation
YopM Yersinia species Interaction with PRK2 and RSK1 kinases Cytotoxicity
SptP S. typhimurium Inhibition of the MAP kinase pathway
Enhancement of Salmonella capacity to
induce TNF-alpha secretion
ExoU P. aeruginosa Lysophospholipase A activity Lung injury

62. Toxins with unknown mechanism of action
Toxin Organism Activity Consequence
Zot V. cholerae ?
Modification of intestinal tight junction
permeability
Hemolysin
BL (HBL)
B. cereus
Hemolytic, dermonecrotic and
vascular permeability activities
Food poisoning, fluid accumulation and
diarrhea
BSH L. monocytogenes ?
Increased bacterial survival and intestinal
colonization

63. Abbreviations
SEA-SEI, staphylococcal enterotoxins SHT, Shiga toxin;
TSST, toxic shock syndrome toxin PT, pertussis toxin;
SPE, streptococcal exotoxin CT, cholera toxin;
SSA, streptococcal superantigen LT, heat-labile enterotoxin;
SMEZ, streptococcal mitogenic exotoxin z DNT, dermonecrotic toxin;
MAM, Mycoplasma arthritidis mitogen CDT, cytolethal distending toxin;
YPMa, Y. pseudotuberculosis-derived mitogen TeNT, tetanus neurotoxin;
ETA and ETB, exfoliative toxins RTX, repeats in the structural toxin;
ColH, collagenase Hly, hemolysin;
Nhe, nonhemolytic entertoxin Cry, crystal;
PFO, perfringolysin O; BoNT, botulinum neurotoxin;
SLO, streptolysin O; Ipa, invasion plasmid antigen;

64. Abbreviations
LLO, listeriolysin O; Sip, Salmonella invasion protein;
ALO, anthrolisin O; EDIN, epidermal cell differentiation inhibitor;
AT, α-toxin; Sop, Salmonella outer protein;
PA, protective antigen; Ipg, invasion plasmid gene;
DT, diphtheria toxin; Yop, Yersinia outer protein;
PAETA, Pseudomonas aeruginosa exotoxin A; GAP, GTPase-activating protein;
GAS, group A Streptococcus; Vir, virulence protein;
YpkA, Yersinia protein kinase A; Tir, translocated intimin receptor;
EPEC, enteropathogenic E. coli; CagA, cytotoxin-associated gene A;
SptP, Salmonella protein tyrosine phosphatase; VAMP, vesicle-associated membrane protein;
ICE, interleukin-1β-converting enzyme; SNAP, synaptosome-associated protein;
MAPKK, mitogen-activated protein kinase ; Zot, zonula. occludens toxin; and BSH, bile salt hydrolase.

65. Enzymatic activities
Glucosyl-transferases
Deamidases
ADP-ribosyltransferases
N-Glycosidases
Metalloproteases

66. DT Elongation factor EF-2 Cell death
PAETA Elongation factor EF-2 Cell death
PT Gi, Go and transducin
CT
Gs, Gt and Golf
cAMP increase
E. coli LT
Clostridium botulinum C2 Actin Failure in actin
P. aeruginosa ExoS Ras Collapse of cytoskeleton
Clostridium botulinum C3 Rho
Breakdown of cellular actin stress
fibers
ADP-ribosyltransferases Toxin Substrate Effect

67. Clostridium difficile toxins A and B Rho/Ras GTPases Breakdown of cytoskeletal structure
Toxin Substrate Effect
Glucosyl-transferases
Deamidases
E. coli CNF1 Rho, Rac and CdC42
Bordetella DNT Rho,
Stress fiber formation
Shiga toxin Ribosomal RNA
Disruption of normal homoeostatic
functions
N-Glycosidases
Metalloproteases
Bacillus anthracis LF Macrophages
Clostridium tetanii TeNT VAMP/synaptobrevin Spastic paralysis
Flaccid paralysis
C. botulinum BoNTs VAMP/synaptobrevin, SNAP-25
Stop of protein synthesis

68. Abbreviations
SNAP-25, synaptosome-associated protein of 25 kDa. CNF1, cytotoxin necrotizing factor 1;
DNT, dermonecrotic factor; DT, diphtheria toxin;
PAETA, Pseudomonas aeruginosa exotoxin A; PT, pertussis toxin;
CT, cholera toxin; LT, heat-labile enterotoxin;
ExoS, exoenzyme S; LF, lethal factor;
TeNT, tetanus neurotoxin; BoNT, botulinum neurotoxin;
VAMP, vesicle associated membrane protein;

69. Thank You